Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:

Number of Participants With Unacceptable Toxicity [ Time Frame: After all patients have completed therapy, up to 1 year after last patient is enrolled ] [ Designated as safety issue: Yes ]

Objective: To study the feasibility of combining: 1) bevacizumab with cisplatin, doxorubicin, and high-dose methotrexate (MAP) in patients with localized resectable osteosarcoma; and 2) bevacizumab with MAP and ifosfamide, and etoposide in patients with unresectable or metastatic osteosarcoma.

A six-stage group sequential stopping rule was developed for monitoring unacceptable toxicity.

3-Year Event Free Survival Compared to Historical Controls on the Intergroup Study 0133 [ Time Frame: After all patients have completed therapy, up to 4 years after last patient is enrolled ] [ Designated as safety issue: No ]

To study the effect of adding bevacizumab to chemotherapy comprised of cisplatin, doxorubicin, and HDMTX on the event-free survival (EFS) in patients with localized resectable osteosarcoma compared to historical controls treated with cisplatin, doxorubicin, and HDMTX without bevacizumab on the Intergroup Study 0133.

Secondary Outcome Measures:

Histologic Response by Stratum [ Time Frame: After 6 cycles of chemotherapy, up to 1 year after the start of therapy ] [ Designated as safety issue: No ]

The effect of adding bevacizumab to preoperative chemotherapy comprised of cisplatin, doxorubicin, and HDMTX on the histologic response in patients with localized resectable osteosarcoma compared to historical controls treated with preoperative cisplatin, doxorubicin, and HDMTX without bevacizumab on the Intergroup Study 0133.

Histologic response at week 10 of therapy was evaluated by Huvos grading systems as grade I: tumor not responding to therapy, no effect identified; grade IIA: more than 50% viable tumor left; grade IIB: 5-50% viable tumor remaining; grade III: only scattered foci of viable tumor seen (less than 5% of tumor); grade IV: no viable tumor seen in extensive sampling (at least a full cross-section of the tumor).

The study did not enroll an adequate number of participants, therefore, the comparison to Intergroup Study 0133 participants was not done.

2-Year Event Free Survival (EFS) of Patients With Osteosarcoma [ Time Frame: After all patients have completed therapy, up to 2 years after last patient is enrolled ] [ Designated as safety issue: No ]

Kaplan-Meier method was used to estimate the EFS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.

2-Year Overall Survival (OS) of Patients With Osteosarcoma [ Time Frame: After all patients have completed therapy, up to 2 years after last patient is enrolled ] [ Designated as safety issue: No ]

Kaplan-Meier method was used to estimate the OS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.

2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol. [ Time Frame: After all patients have completed therapy, up to 2 years after last patient is enrolled ] [ Designated as safety issue: No ]

The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS20008 to that of OS99 (NCT00145639) participants was not done. The 2-year EFS of OS2008 participants is reported here.

2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol. [ Time Frame: After all patients have completed therapy, up to 2 years after last patient is enrolled ] [ Designated as safety issue: No ]

The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS2008 to that of OS99 (NCT00145639) participants was not done. The 2-year OS of OS2008 participants is reported here.

Other Outcome Measures:

Number of Participants With Neuropathic Pain (NP) Following Surgery [ Time Frame: Up to 6 months postoperatively ] [ Designated as safety issue: No ]

Of the 43 participants enrolled on this trial, 37 met criteria for evaluation of neuropathic pain (NP) following definitive surgery. The 37 participants underwent 38 surgeries: one participant had a limb-sparing surgery followed by an amputation surgery. Six of 43 participants were excluded from evaluation for NP: 1 due to deep vein thrombosis, 2 removed from study prior to surgery, 1 removed immediately after surgery to receive radiation therapy, 1 had non-extremity osteosarcoma, and 1 patient had a fibula resection. Patients were followed for neuropathic pain daily for the first week postoperatively and weekly for up to 6 months postoperatively.

Median Duration of Neuropathic Pain [ Time Frame: From surgery until resolution of NP symptoms, up to 6 months ] [ Designated as safety issue: No ]

Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.

Mean Duration of Neuropathic Pain [ Time Frame: From surgery until resolution of NP symptoms, up to 6 months ] [ Designated as safety issue: No ]

Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.

Median Duration of Neuropathic Pain Medication [ Time Frame: From surgery until resolution of NP symptoms, up to 6 months ] [ Designated as safety issue: No ]

Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.

Mean Duration of Neuropathic Pain Medication [ Time Frame: From surgery until resolution of NP symptoms, up to 6 months ] [ Designated as safety issue: No ]

Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.

Participants with localized resectable disease receive Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin, and doxorubicin, or methotrexate. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, or methotrexate.

Participants with metastatic disease (Stratum B) receive Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin and doxorubicin, methotrexate or ifosfamide, and etoposide. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, methotrexate, or ifosfamide, and etoposide. Radiotherapy will be given post-operatively.

Participants with unresectable disease (Stratum C) receive treatment identical to Stratum B: Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin and doxorubicin, methotrexate or ifosfamide, and etoposide. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, methotrexate, or ifosfamide, and etoposide. Radiotherapy will be given post-operatively.

This is a comprehensive study that uses a novel agent that targets angiogenesis (bevacizumab) in combination with conventional chemotherapy for the treatment of osteosarcoma. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), has been shown to stop the growth of new blood vessels of tumors, both in the laboratory and in patients with other types of cancers. Bevacizumab has improved the effect of chemotherapy in adult patients with different types of cancer by increasing tumor response and increasing the chances of survival. This study has two main goals:

To find out if bevacizumab can be combined safely with chemotherapy for osteosarcoma

To find out if adding bevacizumab to chemotherapy will be beneficial in treating osteosarcoma.

The chemotherapy drugs used in this study are commonly used to treat osteosarcoma. Patients with non-metastatic and resectable tumors receive bevacizumab and chemotherapy comprised of cisplatin, doxorubicin and high-dose methotrexate. Patients with metastatic tumors or tumors that cannot be removed by surgery receive bevacizumab and chemotherapy comprised of cisplatin, doxorubicin and high-dose methotrexate, ifosfamide and etoposide. If the tumor can be removed by surgery, surgery will be performed after 10 weeks of chemotherapy and will be followed by additional chemotherapy. After completion of active therapy, patient's response to therapy will be followed for approximately 5 years.

Eligibility

Ages Eligible for Study:

up to 30 Years (Child, Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patient must have newly diagnosed high-grade, biopsy proven, osteosarcoma or malignant fibrous histiocytoma (MFH) of bone with no history of prior chemotherapy or radiation;

Participant is able to perform tasks and daily activities as defined in the study guidelines

Patient meets established guidelines for adequate function of the kidney, liver, heart and bone marrow

Participants meets other requirements defined in the eligibility portion of the study

Exclusion Criteria:

recent major surgical procedure or injury

Known bleeding diathesis, platelet disorder or coagulopathy

Thrombosis

Cardiac disease or hypertension

Significant proteinuria

Central nervous system disease

Gastrointestinal perforation/abdominal fistula

Osteosarcoma or MFH of bone as second malignancy

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667342